ADAR2 deficiency ameliorates non-alcoholic fatty liver disease and muscle atrophy through modulating serum amyloid A1.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, which is commonly associated with NAFLD. Adenosine-to-inosine editing, catalysed by adenosine deaminase acting on RNA (ADAR), is an important post-transcriptional modification of genome-encoded RNA transcripts. Three ADAR gene family members, including ADAR1, ADAR2 and ADAR3, have been identified. However, the functional role of ADAR2 in obesity-associated NAFLD and sarcopenia remains unclear. METHODS: ADAR2+/+/GluR-BR/R mice (wild type [WT]) and ADAR2-/-/GluR-BR/R mice (ADAR2 knockout [KO]) were subjected to feeding with standard chow or high-fat diet (HFD) for 20 weeks at the age of 5 weeks. The metabolic parameters, hepatic lipid droplet, grip strength test, rotarod test, muscle weight, fibre cross-sectional area (CSA), fibre types and protein associated with protein degradation were examined. Systemic and local tissues serum amyloid A1 (SAA1) were measured. The effects of SAA1 on C2C12 myotube atrophy were investigated. RESULTS: ADAR2 KO mice fed with HFD exhibited lower body weight (-7.7%, P < 0.05), lower liver tissue weight (-20%, P < 0.05), reduced liver lipid droplets in concert with a decrease in hepatic triglyceride content (-24%, P < 0.001) and liver injury (P < 0.01). ADAR2 KO mice displayed protection against HFD-induced glucose intolerance, insulin resistance and dyslipidaemia. Skeletal muscle mass (P < 0.01), muscle strength (P < 0.05), muscle endurance (P < 0.001) and fibre size (CSA; P < 0.0001) were improved in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. Muscle atrophy-associated transcripts, such as forkhead box protein O1, muscle atrophy F-box/atrogin-1 and muscle RING finger 1/tripartite motif-containing 63, were decreased in ADAR2 KO mice fed with HFD compared with WT mice fed with HFD. ADAR2 deficiency attenuates HFD-induced local liver and skeletal muscle tissue inflammation. ADAR2 deficiency abolished HFD-induced systemic (P < 0.01), hepatic (P < 0.0001) and muscular (P < 0.001) SAA1 levels. C2C12 myotubes treated with recombinant SAA1 displayed a decrease in myotube length (-37%, P < 0.001), diameter (-20%, P < 0.01), number (-39%, P < 0.001) and fusion index (-46%, P < 0.01). Myogenic markers (myosin heavy chain and myogenin) were decreased in SAA1-treated myoblast C2C12 cells. CONCLUSIONS: These results provide novel evidence that ADAR2 deficiency may be important in obesity-associated sarcopenia and NAFLD. Increased SAA1 might be involved as a regulatory factor in developing sarcopenia in NAFLD.

Highly Efficient Room Temperature NO2 Sensor Using Two-Phase TiOx Heterogeneous Nanoparticles.

In this study, we successfully synthesized two-phase titanium oxide (TiOx) heterogeneous nanoparticles (NPs) using an advanced sol-gel method, a significant stride in developing efficient, room temperature (RT) NO2 gas sensors. The prepared two-phase TiOx heterogeneous NPs exhibited exceptional sensitivity to low concentrations of NO2 gas at RT. The heightened gas response was attributed to a significant presence of oxygen vacancies, creating intermediate states within the two-phase heterostructures and thus narrowing the band gap. This facilitated electron transport from the valence band (VB) to the conduction band (CB), resulting in increased current at RT. The XPS analysis confirmed a substantial amount of chemisorbed oxygen O2(ads)- within the two-phase heterostructures, providing more chemisorption sites for nitrogen dioxide gas. This increase in chemisorption sites significantly improved the gas response. Furthermore, the introduction of zinc into the TiOx NPs reduced their band gap, enhancing the background resistance signal-to-noise ratio and increasing the response while maintaining remarkable stability. In summary, our work introduces a promising RT NO2 sensor based on two-phase TiOx heterogeneous NPs, holding great potential for applications in environmental monitoring and gas sensing technology. In future work, we aim to delve deeper into the capabilities of the sensor, exploring broader applications and refining its design for enhanced practicality in environmental monitoring.

Crosslinking kiwifruit-derived DNA with natural aromatic aldehydes generates membranolytic antibacterial nanogels.

Improper use of antibiotics has led to the global rise of drug-resistant biofilm bacteria. Thus, researchers have been increasingly interested in green materials that are highly biocompatible and have low toxicity. Here, nanogels (NGs) with imine bonds were synthesized by crosslinking kiwifruit-derived DNA's primary amine and aromatic aldehydes (cuminaldehyde, p-anisaldehyde, or vanillin) under water-in-hexane emulsion processes. Transmission electron microscope showed that the NGs had spherical geometry with an average particle size ranging from 40 to 140 nm and that the zeta potential indicated a negative charge. Additionally, the DNA-aromatic aldehyde NGs showed low cytotoxicity toward normal cell organoids and human RBCs in cell viability tests. These NGs were also tested against four pathogenic bacteria for various assays. DNA-vanillin (DNA-VA) NGs exhibited significant antibacterial effects against bacteria with very low inhibitory concentrations as seen in a minimum inhibitory concentration assay. Scanning electron microscope observation revealed that the bacteria were deformed, and immunoblotting detected intracellular groEL protein expression. In agreement with these results, DNA-aromatic aldehyde NGs successfully protected C. elegans from P. aeruginosa-induced lethality. These DNA NGs provided a multivalent 3D space for antibacterial aromatic aldehydes to tether, enhancing their interaction with the bacterial wall. These results offer a new direction for the development of novel antibiotics in the future.